Animal Models for Salmonellosis: Applications in Vaccine Research

Abstract

Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.A nimal models are indispensable tools for assessing candidate vaccines, with preclinical animal safety, immunogenicity, and efficacy data being prerequisite for regulatory agencies such as the U.S. Food and Drug Administration (FDA) prior to undertaking early-stage clinical trials. However, not all animal models are created equal. While some models are highly robust and closely mimic clinical infection, others are contrived and far removed from clinical relevance. Choosing the right animal model for the vaccine under investigation is imperative in determining its safety and/or effectiveness.Salmonella spp. are often used as model organisms to study bacterial pathogenesis and host-microbe interactions, due to the ability of certain Salmonella serovars to readily infect animals. As such, there are a myriad of animal models available to vaccine developers. These range from colonization or lethality models to those involving complex surgical techniques (Table 1). The choice of model is often related not only to relevance but also cost, ethics, housing requirements, and the availability of appropriate technical expertise. While most researchers utilize one model or another, integration of data from multiple animal models can provide a more complete understanding of the safety of a candidate vaccine and/or predict how a potential vaccine may perform in humans. In this minireview, we provide background on Salmonella clinical syndromes and pathogenesis and then summarize the various animal models that have been used for Salmonella vaccine research. We include a brief discussion of the technical aspects, advantages, and limitations of each model, followed by a review of the literature surrounding its use in vaccine evaluation. While there has been considerable development for veterinary Salmonella vaccines, here we will focus solely on vaccines and models for human salmonellosis.

Efficacy of chitosan-based nanoparticle vaccine administered to broiler birds challenged with Salmonella

“…S. Heidelberg has been isolated from poultry products in Brazil since 1962, while S. Enteritidis is a severe problem in poultry and public health since 1993 [5]. Upon ingestion, Salmonella will survive passage through the low-pH conditions of the stomach [6,7], stimulate macrophages, and evade killing by the host immune system [8]. Within a few hours, Salmonella can invade the intestinal tract and reach the liver and spleen, and Salmonella can colonize the ceca in chickens [9].…”

Improved Tolerability of a Salmonella enterica Serovar Typhimurium Live-Attenuated Vaccine Strain Achieved by Balancing Inflammatory Potential with Immunogenicity

“…This may be due to a balance between attenuation and the capacity to engage immune components and trigger a controlled proinflammatory response by the more refined strain. While, in general, strains that are more attenuated are less immunogenic (19), the combination of mutations in CVD 1926 may render this strain better equipped to induce adaptive immunity. The antibodies induced were also long lasting, with titers lasting for at least 3 months after the final immunization.…”

Evaluation of alum-based adjuvant on the immunogenicity ofsalmonella entericaserovar typhi conjugates vaccines

“…29 However, the infection of Salmonella enterica serovar Typhimurium produces clinical outcomes that are different from human NTS gastroenterities. 31 Therefore, the capability of TCV to offer sterile protection was evaluated via the analysis of CD4 C cytokine production and not by the animal challenge. The mice vaccinated with TCV formulated in adjuvant AlOH expressed higher levels of IL4 than the groups receiving another vaccine.…”